Insecticidal agents and compositions have been developed to control insect pests such as agrohorticultural pests, hygienic pests, or wood-eating pests and in practice have been used as a single or a mixed agent. However, economically efficient and ecologically safe insect control compositions are still being sought. Insecticidal compositions which allow for reduced effective dosage rates, increased environmental safety and lower incidence of insect resistance are highly desirable. Although the rotational application of insect control agents having different modes of action may be adopted for good pest management practice, this approach does not necessarily give satisfactory insect control. Further, even though combinations of insect control agents have been studied, a high synergistic action has not always been found. Obtaining an insecticidal composition which demonstrates no cross-resistance to existing insecticidal agents, no toxicity problems and little negative impact on the environment is extremely difficult.
Therefore, it is an object of this invention to provide a synergistic insecticidal composition which demonstrates a high controlling effect with concomittant reduced crop production cost and reduced environmental load.
It is another object of this invention to provide methods for synergistic insect control and enhanced crop protection.
The present invention provides a synergistic insecticidal composition comprising as essential active ingredients a synergistically effective amount of a neuronal sodium channel antagonist in combination with one or more compounds selected from the group consisting of pyrethroids, pyrethroid-type compounds, recombinant nucleopolyhedroviruses capable of expressing an insect toxin, organophosphates, carbamates, formamidines, macrocyclic lactones, amidinohydrazones, GABA (gamma-aminobutyric acid) antagonists, and acetylcholine receptor ligands.
The present invention also provides a method for synergistic insect control which comprises contacting said insect with a synergistically effective amount of a neuronal sodium channel antagonist in combination with one or more compounds selected from the group consisting of pyrethroids, pyrethroid-type compounds, recombinant nucleopolyhedroviruses capable of expressing an insect toxin, organophosphates, carbamates, formamidines, macrocyclic lactones, amidinohydrazones, GABA antagonists and acetylcholine receptor ligands.
The present invention further provides a method for the enhanced protection of plants from infestation and attack by insects.
Definitions
xe2x80x9cAcetylcholine receptor ligand compoundxe2x80x9d as used in this application means a compound which is capable of binding to the acetylcholine receptor site.
xe2x80x9cGroup Axe2x80x9d as used in this application means insecticidal
1) pyrethroid compounds;
2) pyrethroid-type compounds;
3) recombinant nucleopolyhedroviruses capable of expressing an insect toxin;
4) organophosphate compounds;
5) carbamate compounds;
6) formamidine compounds;
7) macrocyclic lactone compounds;
8) amidinohydrazone compounds;
9) GABA antagonist compounds; and
10) acetylcholine receptor ligand compounds.
xe2x80x9cHaloalkylxe2x80x9d as used in this application means an alkyl group CxH2x+1 having 1 to 2x+1 halogen atoms which may be the same or different. Similarly, the terms xe2x80x9chaloalkenylxe2x80x9d, xe2x80x9chaloalkynylxe2x80x9d, xe2x80x9chaloalkoxyxe2x80x9d, xe2x80x9chalophenylxe2x80x9d and the like mean mono- to perhalogen substitution wherein the halogens may be the same or different.
xe2x80x9cHalogenxe2x80x9d as used in this application means Cl, Br, I or F.
xe2x80x9cNeuronal sodium channel antagonistxe2x80x9d as used in this application means a compound which is capable of preventing the ability of a neuron cell to transfer sodium ions across the cell membrane.
xe2x80x9cPyrethroid-type compoundsxe2x80x9d as used in this application means those compounds characterized by a non-ester linked aryl-phenoxybenzyl moiety.
xe2x80x9cSynergismxe2x80x9d as used in this application means a cooperative action encountered in a combination of two or more biologically active components in which the combined activity of the two or more components exceeds the sum of the activity of each component alone.
Surprisingly, it has now been found that a composition which comprises a combination of a neuronal sodium channel antagonist and a second insecticidal ingredient provides superior insect control at lower levels of the combined active agents than may be achieved when the neuronal sodium channel antagonist or the second insecticidal ingredient is applied alone.
As previously stated, the term neuronal sodium channel antagonist designates a compound which is capable of preventing the ability of a neuron cell to transfer sodium ions across the cell membrane. A neuron cell thus affected is unable to fire, resulting in paralysis, and ultimately mortality, in the target host. Descriptions of neuronal sodium channel antagonists and their mode of action may be found in Pesticide Biochemistry and Physiology, 60: 177-185 or Archives of Insect Biochemistry and Physiology, 37: 91-103.
Neuronal sodium channel antagonists include compounds such as those described in U.S. Pat. Nos. 5,543,573; 5,708,170; 5,324,837 and 5,462,938, (the description of which are hereby incorporated by reference) among other publications. Exemplary of the neuronal sodium channel antagonist compounds useful in the composition of this invention are those compounds having the structural formula 
wherein A is CR4R5 or NR6;
W is O or S;
X, Y, Z, Xxe2x80x2, Yxe2x80x2 and Zxe2x80x2 are each independently H; halogen; OH; CN; NO2; C1-C6alkyl optionally substituted with one or more halogen, C1-C3alkoxy, C1-C3haloalkoxy, C3-C6cycloalkyl, C2-C6alkenyloxy or sulfonyloxy groups; C1-C6 alkoxy optionally substituted with one or more halogen, C1-C3alkoxy or C3-C6cycloalkyl groups; C1-C6alkoxycarbonyl, C3-C6cycloalkylcarbonyloxy, phenyl optionally substituted with one or more halogen, C1-C4 alkyl, or C1-C4 alkoxy groups; aminocarbonyloxy optionally substituted with one or more C1-C3alkyl groups; C1-C6alkoxycarbonyloxy; C1-C6alkylsulfonyloxy; C2-C6 alkenyl; or NR12R13;
m, p and q are each independently an integer of 1, 2, 3, 4, or 5;
n is an integer of 0, 1 or 2;
r is an integer of 1 or 2;
t is an integer of 1, 2, 3 or 4;
R, R1, R2, R3, R4 and R5 are each independently H or C1-C4alkyl;
R6 is H, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxyalkyl, C1-C6alkoxy, C1-C6haloalkoxy, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkylcarbonyl, C1-C6alkoxy-carbonyl, C1-C6alkylthio, or C1-C6haloalkylthio;
R7 and R8 are each independently H; halogen; C1-C6alkyl; C1-C6alkylcarbonyloxy; or phenyl optionally substituted with one or more halogen, CN, NO2, C1-C6alkyl, C2-C6haloalkyl, C1-C6alkoxy or C1-C6haloalkoxy groups;
R9 and R10 are each independently H, or C1-C4alkyl;
R11 is H, C1-C6alkyl, C1-C6haloalkyl, C1-C4alkyl-carbonyl, C1-C6alkoxycarbonyl, or C1-C6halo-alkoxycarbonyl;
R12 and R13 are each independently H or C1-C6alkyl;
G is H; C1-C6alkyl optionally substituted with one or more halogen, C1 -C4alkoxy, C1-C6haloalkoxy, CN, NO2S(O)uR14, COR15, CO2R16, phenyl or C3-C6cycloalkyl groups; C1-C6alkoxy; C1-C6haloalkoxy; CN; NO2; S(O)uR17; COR18; CO2R19; phenyl optionally substituted with one or more halogen, CN, C1-C3halo-alkyl, or C1-C3haloalkoxy groups; C3-C6cycloalkyl; or phenylthio;
Q is phenyl optionally substituted with one or more halogen, CN, SCN, NO2, S(O)uR20, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxyalkyl, C1-C6alkoxy, C1-C6haloalkoxy, or NR21R22 groups;
u is an integer of 0, 1 or 2;
R14, R15, R16, R18, R19, R21 and R22 are each independently H or C1-C6alkyl;
R17 and R20 are each independently C1-C6alkyl or C1-C6haloalkyl;
R33 is CO2R34;
R34 is H, C1-C6alkyl, C1-C6haloalkyl, phenyl or halophenyl; and the dotted line configuration C{overscore (--)}N represents a double bond or a single bond (i.e. Cxe2x80x94N or Cxe2x95x90N); or
a stereoisomer thereof.
Preferred neuronal sodium channel antagonists suitable for use in the composition of the invention are those compounds of formula I, II or III wherein the dotted line configuration C{overscore (--)}N represents a double bond.
More preferred neuronal sodium channel antagonists suitable for use in the inventive composition are those compounds of formula I or formula III wherein the dotted line configuration represents a double bond.
Particularly preferred neuronal sodium channel antagonists useful in the composition of the invention are those compounds of formula I or formula III wherein W is O; X is trifluoromethoxy and is in the 4-position; Y is trifluoromethyl and is in the 3-position; Z is CN and is in the 4-position; A is CH2; n is 0; m, p and q are each 1; R and R1, are each H; Z is C1; R33 and G are each CO2CH3; Q is p-(trifluoromethoxy)phenyl; and the dotted line configuration C{overscore (--)}N represents a double bond; or a stereoisomer thereof.
Further neuronal sodium channel antagonist compounds include those described in U.S. Pat. Nos. 5,116,850 and 5,304,573, (the description of which are hereby incorporated by reference) among other publications. Exemplary of further neuronal sodium channel antagonist compounds suitable for use in the composition of the invention are those compounds having structural formula 
wherein W is O or S;
Xxe2x80x3 and Yxe2x80x3 are each independently H; halogen; CN; SCN; C1-C6alkyl optionally substituted with one or more halogen, NO2, CN, C1-C4alkoxy, C1-C4alkylthio, phenyl, halophenyl, C1-C4alkylsulfonyl, C1-C4haloalkylsulfonyl, or C1-C4alkoxycarbonyl groups; C2-C4alkenyl; C2-C4haloalkenyl; C2-C4alkynyl; C2-C4haloalkynyl; C3-C6cycloalkyl; C3-C6halocyclo-alkyl; phenyl optionally substituted with one or more halogen, CN, NO2, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy, C1-C4alkylthio, C1-C4alkylsulfonyl or C1-C4haloalkylsulfonyl groups; C1-C4alkylcarbonyl; C1-C4haloalkylcarbonyl; or NR28R29;
m is an integer of 1, 2, 3, 4 or 5;
Gxe2x80x2 is phenyl optionally substituted with one or more groups which may be the same or different selected from Xxe2x80x3 ; a 5-membered heteroaromatic ring containing one or two heteroatoms selected from 0 or 1 oxygen, 0 or 1 sulfur and 0, 1 or 2 nitrogen atoms said 5-membered heteroaromatic ring being attached via carbon and being optionally substituted with one or more groups which may be the same or different selected from X; or a 6-membered heteroaromatic ring containing one or two heteroatoms selected from 0 or 1 oxygen, 0 or 1 sulfur and 0, 1 or 2 nitrogen atoms said 6-membered heteroaromatic ring being attached via carbon and being optionally substituted with one or more groups which may be the same or different selected from Xxe2x80x3;
Qxe2x80x2 is H; C1-C6alkyl optionally substituted with one or more halogen, CN, C1-C3alkoxy, C1-C6alkoxycarbonyl, or phenyl optionally substituted with one or more halogen, CN, NO2, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkylsulfonyl or C1-C4alkyl-sulfinyl groups; C2-C6alkenyl; C2-C6alkynyl; or phenyl optionally substituted with one to three groups, which may be the same or different, selected from Xxe2x80x3;
R23, R24, R25, R26, R27, R28 and R29 are each independently H or C1-C4alkyl; and the dotted line configuration C{overscore (--)}N represents a double bond or a single bond (i.e. Cxe2x80x94N or Cxe2x95x90N); or a stereoisomer thereof.
Further preferred neuronal sodium channel antagonist compounds of the invention are those compounds of formula IV or V wherein the dotted line configuration C{overscore (--)}N represents a double bond.
Other preferred neuronal sodium channel antagonist compounds suitable for use in the composition of the invention are those compounds of formula IV or V wherein W is O ; Xxe2x80x3 and Yxe2x80x3 are each independently H or C1-C6halo-alkyl; m is 1; R23, R24, R25, R26 and R27 are each H; G is phenyl optionally substituted with one or more halogen atoms; Qxe2x80x2 is halophenyl or C1-C4alkyl optionally substituted with one phenyl or halophenyl group; and the dotted line configuration Cxe2x95x90N represents a double bond; or a stereoisomer thereof.
The second active ingredient of the insecticidal composition of the invention includes one or more compounds selected from Group A:
1) pyrethroid compounds which are known to be insecticidally active such as cypermethrin, cyhalothrin, cyfluthrin, permethrin or the like;
2) pyrethroid-type compounds which are known to be insecticidally active such as ethofenprox, silafluofen, or the like;
3) recombinant nucleopolyhedroviruses capable of expressing an insect toxin, preferably an insect neurotoxin such as Androctonus australis insect toxin (AaIT), for example HzNPV-AaIT;
4) organophosphate compounds which are known to be insecticidally active such as profenofos, acephate, sulprofos, malathion, diazinon, methyl parathion, terbufos, or the like;
5) carbamate compounds which are known to be insecticidally active such as methomyl, thiodicarb, fenothiocarb, or the like;
6) formamidine compounds which are known to be insecticidally active such as amitraz, chlordimeform, hydramethylnon, chlorfenamidine, or the like;
7) macrocyclic lactone compounds which are known to be insecticidally active such as spinosad, avermectin, emamectin, milbemectin, nemadectin, moxidectin or the like;
8) amidinohydrazone compounds which are known to be insecticidally active such as hydramethylnon;
9) GABA antagonist compounds which are known to be insecticidally effective such as fipronil, endosulfan, or the like;
10) acetylcholine receptor ligand compounds which are known to be insecticidally effective such as imidacloprid, acetamiprid, nitenpyram, thiamethoxam, or the like.
Descriptions of the above-listed commercially available compounds may be found in The Pesticide Manual, 11th Edition, British Crop Protection Council (1997)among other publications. Descriptions of recombinant nucleopolyhedroviruses capable of expressing an insect toxin include Treacy et al, Proceedings Beltwide Cotton Conference (1999), pp 1076-1083.
Preferred compositions of the invention are those compositions having a neuronal sodium channel antagonist compound of formula I or formula III in combination with one or more compounds selected from Group A.
More preferred compositions of the invention are those compositions having a formula I or formula III compound wherein W is O; X is trifluoromethoxy and is in the 4-position; Y is trifluoromethyl and is in the 3-position; Z is CN and is in the 4-position; A is CH3; n is 0; m, p and q are each independently 1; R and R1 are each independently H; Zxe2x80x2 is Cl; R33 and G are each independently CO2CH3; Q is p-(trifluoromethoxy)phenyl; and the dotted line configuration Cxe2x95x90N represents a double bond in combination with one or more compounds selected from Group A.
Each of the compounds of formula I, II, III, IV and V embody assymetric centers which may be represented in the stereoisomeric R-form or S-form. The present invention also includes the R-form, the S-form or mixtures comprising the R-form and the S-form in an arbitrary ratio. For compounds of formula III, the S-form is preferred.
Advantageously, the neuronal sodium-channel antagonist compound of formula I, II, III, IV or V or a mixture thereof may be formulated with a second insecticidally effective ingredient and optionally other customary formulation adjuvants. Said formulation may be dispersed in a solid or liquid diluent for application to the insect, its food supply, breeding ground or habitat as a dilute spray or as a solid dust or dust concentrate.
The active ingredients of the inventive composition may also be formulated separately as a wettable powder, emulsifiable concentrate, aqueous or liquid flowable, suspension concentrate or any one of the conventional formulations used for insect control agents and tank-mixed in the field with water or other inexpensive liquid for application as a liquid spray mixture. The separately formulated compositions may also be applied sequentially.
Advantageously, the composition of the invention may be formulated as a bait composition comprising a synergistically effective amount of a combination of a neuronal sodium channel antagonist plus one or more compounds selected from Group A and a solid or liquid edible nutritive substance. A preferred bait composition may contain by weight about 0.01% to 20% active ingredients, preferably a neuronal sodium channel antagonist in combination with hydramethylnon.
In actual practice, the composition of the invention may be applied to the plant foliage or plant stem or to the insect habitat or to the locus of a hygienic pest as a dilute spray prepared from any of the above-said formulations. The ratio of the essential active ingredients of the composition of the invention is about 1 weight part of a neuronal sodium channel antagonist to about 0.01-100 weight parts of one or more compounds selected from Group A.
The compositions of the invention are superior insecticidal compositions and are especially useful for the control of agrohorticultural pests, hygienic pests or wood-eating pests. Said compositions are highly effective for the protection of growing and harvested plants including: leguminous crops such as soybeans, snap beans, peas, wax beans and the like as well as cotton, forage crops, cole crops, leafy vegetables, tobacco, hops, tomatoes, potatoes, flowering ornamentals such as chrysanthemums, vine crops such as grapes, squash, pumpkin or melon and fruit trees such as cherry, peach, apple or citrus, from the ravages of insects.
The synergistic insecticidal composition of the invention is found to be highly active against a wide variety of lepidopteran and coleopteran insects such as Helicoverpa zea (cotton bollworm), Heliothis virescens (tobacco budworm), Leptinotarsa decemlineata (Colorado potato beetle), Diabrotica spp. (corn rootworm) and the like.
Beneficially, the composition of the invention may be useful for the prevention and control of hygienic or public health pests such as: Diptera, e.g. houseflies, mosquitoes, or the like; Hymenoptera, e.g. ants, parasitic wasps, wasps or the like; Blattaria, e.g. cockroaches; or the like.
Further, the compositions of the invention may be particularly useful for the prevention and control of wood-eating insects such as termites (Isoptera), carpenter ants (Hymenoptera), wood-destroying beetles (Coleoptera) or the like.
These and other advantages of the invention may become more apparent from the examples set forth herein below. These examples are provided merely as illustrations of the invention and are not intended to be construed as a limitation thereof.